The purpose of this Core resource is to support the development and application of instrumentation and mathematical tools for Program investigators' studies. The Core will provide state-of-the-art biomagnetic measuring devices, high-resolution electrode arrays, voltage-sensitive-dye and birefringence/fiber-optic recording systems, isolated tissue support systems, and access to extensive computer resources. Technologies to address the behavior of the multidimensional and highly anisotropic cardiac syncytium and its responses to drugs will be developed here and implemented in Project 1. These include biomagnetic measurements of action currents in multidimensional preparations with a high-resolution superconducting QUantum Interference Device (SQUID) magnetometer and analysis of action potential wavefronts with a new recording array having millimeter electrode separations. Recently-developed electrode arrays and fiber-optic recording systems are compatible with operation of the SQUID. These devices make it possible to simultaneously map the extracellular potential, transmembrane potential and net action current, respectively. These data will be used to determine the anisotropic electrical conductivities of the intracellular and extracellular spaces and their responses to various interventions. In axisymmetric preparations, toroidal pickup coils and low-noise amplifiers will be used to determine the action current and thereby the longitudinal resistivity and its response to stretch (Project 5). The computer resources of the Core will be used in numerically-intensive fitting of complex state models to experimentally acquired voltage clamp data (Projects 2 and 3). The anisotropic bidomain model used for analyzing 1- dimensional propagation in earlier studies will be expanded. Non-linear propagating models will be further developed, and will be extended to include cellular discontinuities. The availability of the resource of this Core will allow the Program to pursue lines of investigation which would otherwise be unavailable.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Vanderbilt University Medical Center
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Yang, Tao; Smith, Jarrod A; Leake, Brenda F et al. (2013) An allosteric mechanism for drug block of the human cardiac potassium channel KCNQ1. Mol Pharmacol 83:481-9
Hayashi, Kenshi; Shuai, Wen; Sakamoto, Yuichiro et al. (2010) Trafficking-competent KCNQ1 variably influences the function of HERG long QT alleles. Heart Rhythm 7:973-80
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